tbuckley/cabot-search huggingface dataset:
Abstract 11005: The Impact of Time Censoring on Machine Learning Models Which Identify Patients With Undiagnosed Cardiac Amyloidosis
Authors: Greg Lee, Sam Fielden, Brendan Carry, Alvaro Ulloa Cerna, Linyuan Jing, Arun Nemani, Daniel Rocha, Kyle Flick, Jeffrey Ruhl, Jagadish Venkataraman, Noah Zimmerman, Ruijun Chen, Brandon Fornwalt, Christopher M Haggerty
Journal: Circulation (2022)

Introduction: Cardiac amyloidosis (CA) is a common cause of progressive heart failure. New therapies can improve outcomes but most CA patients remain undiagnosed and untreated. Machine learning models deployed on electronic health record (EHR) data may be able to find patients with undiagnosed CA. To date, most models have focused on identification of undiagnosed amyloid from uncensored data modalities (Fig 1). Hypothesis: We hypothesized that lack of post-diagnosis censoring when training CA models leads to poor performance in predicting patients with undiagnosed CA whereas training with appropriate time censoring improves performance. Methods: We used 41 EHR features (demographics, labs, electrocardiogram/echocardiography measurements, vitals) to train a boosted decision tree model with and without time censoring. This was applied to 112 patients with confirmed CA and 22,400 controls matched on age, sex, encounter frequency and timespan of EHR. We also compared our findings to a web-based CA algorithm that was publicly available in 2020. Results: The EHR algorithm had modestly higher performance on at-risk, time-censored patients when trained with and without time censoring (area under the receiver operating characteristic curve (AUROC) 0.84±0.09 vs 0.79±0.07). Testing on temporally uncensored data showed higher performance (AUROC: 0.91±0.05) which may be unrepresentative of deployment scenarios where post-diagnostic features are unavailable for model use. The publicly available algorithm demonstrated a similar trend when tested on uncensored data (AUROC: 0.67±0.03) as compared to an appropriately censored feature set (AUROC: 0.54±0.04). Conclusions: EHR algorithms can be trained to find patients with high risk of undiagnosed cardiac amyloidosis. These models should be evaluated on temporally censored data so that post-diagnostic features do not artificially inflate performance estimates and negatively impact real-world deployment.
Abstract 10710: Plasma Proteomic Profiles of the Blood Pressure Response During Exercise Are Associated With Incident Hypertension
Authors: Prashant Rao, Michelle Keyes, Michael Mi, Jacob Barber, Usman A Tahir, Shuliang Deng, Clary Clish, Dongxiao Shen, Laurie Farrell, Vanessa Xanthakis, Vasan S Ramachandran, Claude Bouchard, Mark A Sarzynski, Robert E Gerszten, Jeremy Robbins
Journal: Circulation (2022)

Introduction: The blood pressure (BP) response during acute exercise (acute exercise blood pressure (AEBP)) is related to future risk of hypertension (HTN) and cardiovascular disease (CVD). Biochemical characterization of AEBP could identify novel biomarkers of CVD risk and inform understanding of its biology. Methods: We applied an aptamer-based proteomics platform to assay ~5000 proteins at rest in 681 healthy individuals of the HERITAGE Family Study (mean age 34y, 54% women) who underwent an acute exercise perturbation. AEBP was measured during submaximal exercise on a cycle ergometer. We then performed a proteomic association study of resting BP and AEBP. Top protein associations with acute exercise SBP and DBP were analyzed for their association with incident HTN and CVD in the Framingham Heart Study (FHS). Putative causal effects of AEBP-related proteins were investigated by Mendelian randomization (MR), using cis-protein quantitative loci genetic instruments. Results: We identified new markers of AEBP, many of which are secreted proteins that span biological processes relevant to vascular function including transforming-growth factor beta-receptor 3 (β = -3.39, p = 2.33e-6), prostaglandin D2-synthase (β = -2.50, p = 1.18e-10-9), and angiopoietin-related protein 4 (β = 2.44, p = 1.05e-4). The addition of 12 AEBP-associated proteins to clinical information informed future risk of HTN and CVD among normotensive community-dwelling individuals (clinical model, clinical proteomic model AUCs: incident HTN 0.69, 0.73; coronary heart disease 0.73, 0.76; heart failure 0.83, 0.87). MR analysis of AEBP-associated proteins supported a potential causal relationship between 5 proteins and BP regulation (TGFBR3, ANGPTL4, CGA FSHB, PTGDS, KLK8). Conclusions: We identified new blood biomarkers of BP regulation that were elicited only by an acute exercise perturbation and highlight novel potential causal pathways.
Abstract 104: Taurine As Biomarker And Therapeutic Target For Cardiac Arrest
Authors: Jing Li, Benjamin L Karfunkle, Cody N Justice, Hajwa Kim, Misha N Granado, Kevin Qin, Chunpei Lee, Pavitra Kotini-Shah, Shaoxia Lin, Xiangdong Zhu, Terry L Vanden Hoek
Journal: Circulation (2022)

Introduction: Out-of-hospital cardiac arrest (CA) is a leading cause of death with high mortality. Most patients die from post-CA syndrome due to ischemia/reperfusion injury-triggered responses. Taurine and glutamate, amino acids with cellular activities that are expressed primarily in heart and brain tissues, respectively, are released in response to CA. Hypothesis: Taurine and glutamate levels in blood reflect the extent of injury of CA. Taurine and glutamate could potentially regulate CA outcomes. Methods: Adult CA patients (n=51, 19 survivors, S and 32 nonsurvivors, NS; 35 received cooling treatment, C while 16 did not, NC) at an urban academic ED were enrolled from 2018-2019. Plasma taurine and glutamate collected at various time points including hospital arrival, 6, 24, 48 and 72 hours after arrival, and measured with commercially available assay kits. In a mouse model, 8-min asystolic cardiac arrest was induced with KCl, followed by initiation of CPR and randomized to blinded administration of taurine (50 mg/kg) or saline placebo at 90 second during CPR. Survival (4h) and mean arterial blood pressure (MAP) were evaluated. The Wilcoxon test and generalized estimating equation were used for comparison at each time point and longitudinal trend analysis for human data. Kaplan-Meier estimate and T-test were used for survival and mean comparison in mice. p &lt;0.05 was considered statistically significant. Results: Plasma taurine and glutamate levels were highest at R0 and decreased over time in both S and NS, and were higher in NS than S. Taurine levels were significantly associated with survival (NS 66.24±41.36 vs. S 37.48±19.46 at 6h, p &lt;0.05) while glutamate levels were not. Taurine levels in both C and NC groups demonstrated a significantly decreasing trend over time, but the C group showed more reduction ( p &lt;0.05), while glutamate levels showed no significant trend. In mice, compared to saline, taurine treatment markedly improved 4h survival and MAP post-ROSC. Conclusions: Decreased release of taurine into blood is correlated with CA survival and may regulate CA outcomes. It has high translational potential as a biomarker for predicting CA survival, guiding cooling treatment, and serving as a therapeutic target to improve CA outcomes.
Abstract 10042: Mental Health Conditions In Congenital Heart Disease: A Danish Population Based Cohort Study
Authors: Kimberley Miles, Nadine A Kasparian, Dora Farkas, Kristina Laugesen, Henrik Toft Sorensen, Nicolas Madsen
Journal: Circulation (2022)

Introduction: We aimed to investigate mental health condition development by 18 years of age among children with congenital heart disease (CHD). Methods: Using Danish health registry data, all children with CHD (n=17,153) were identified from 1996-2017. Mental health conditions were identified using hospital-based diagnoses, medication prescription, and treatment codes during the study period (1996-2019). Children with mental health conditions diagnosed prior to CHD were excluded (n=670, 3.9%). Comparison cohorts included the general population (matched 10:1 for age and sex), siblings of children with CHD, and children with non-CHD major congenital anomalies (MCAs) identified via EUROCAT codes and matched 3:1 for age and sex. Incidence rates per 1,000 person-years, cumulative incidence per 100 persons, and adjusted hazard ratios (aHR [95% CI]) were calculated and stratified by age-based follow-up periods, CHD severity, and sex. Results: The CHD cohort had higher overall rates of mental health conditions than their siblings (aHR 1.41 [1.30-1.52]) and the general population (aHR 1.66 [1.60-1.72]), and when stratified by age periods, CHD severity, and sex (Table 1). The cumulative incidence in the CHD cohort was 35.7% compared with 25.6%, 26.6%, and 35.1% for the general population, sibling, and MCA cohorts, respectively (Figure 1). Conclusions: This population-based cohort study shows that children with CHD are more likely to be diagnosed with mental health conditions by age 18 years than their siblings and the general population, but not children with non-CHD MCAs. Investigation to determine relevant clinical, sociodemographic, and family risk factors is ongoing.
Abstract 11: Community Interventions To Improve Out-of-hospital Cardiac Arrest Survival: Targeting Public Housing Could Be A Solution
Authors: Anne Juul Joergensen, Julie S Kjoelbye, Mads Christian Tofte Gregers, Louise K Jakobsen, Astrid Rolin Kragh, Florian Ettl, Konstantin Krychtiuk, Patrick Sulzgruber, Mario Krammel, Christian Torp-Pedersen, Annette Kjær Ersbøll, Fredrik Folke, Carolina Malta Hansen
Journal: Circulation (2022)

Background: Identifying well-suited areas for community-targeted interventions to improve bystander interventions and OHCA survival, particularly in deprived communities, has been warranted by the AHA. Public housing projects are publicly subsidized, geographically well-defined, have local leadership, and residents typically have a high prevalence of OHCA predictors. To assess the potential reach of community interventions in public housing, we investigated the incidence of OHCA in public housing projects in Vienna (Austria) and Copenhagen (Denmark) and compared it with remaining residential areas. Methods: Non-EMS witnessed OHCAs occurring in residential areas in Vienna (2017-2021) and Copenhagen (2016-2020) were included from the Viennese and Danish Cardiac Arrest Registry, respectively. Population density and residential areas were obtained from Urban Atlas; public housing data from City of Vienna, and the Danish National Building Foundation. We compared OHCA/km 2 and OHCA/100,000 inhabitants between public housing projects and other residential areas using Poisson regression of rates. We calculated the proportion of OHCAs occurring within 100 meters of public housing projects. Results: In Vienna vs. Copenhagen, 32% (1,391/4,313) vs. 35% (817/2,335) of residential OHCAs occur in public housing areas. The relative ratio of OHCA/km 2 and OHCA/100,000 inhabitants is 3-fold and 1.5-fold higher in public housing than in other housing areas, respectively (Figure 1). Including the immediate surroundings, public housing covered 64.8% vs. 56.1% of all residential OHCAs in Vienna and Copenhagen. Conclusion: Public housing projects in Vienna and Copenhagen had a substantially higher incidence of OHCA than other residential areas covering 1/3 of all OHCAs in residential areas and ~60% when including nearby neighborhoods. Community initiatives targeting these areas may be an efficient strategy to improve bystander interventions and survival.
Abstract 10724: Use of Right Heart Catheterization and Length of Stay in Patients With Acute Right Heart Failure: A National Inpatient Database Analysis
Authors: Riddhima Naik, Samir Jha
Journal: Circulation (2022)

Background: Right Heart Catheterization (RHC) is an important tool in the assessment of hemodynamic status in patients with right heart failure (RHF), however is underutilized. Objective: To evaluate the use of RHC in RHF with the primary outcome as mortality and secondary outcome as length of stay (LOS) using the National Inpatient Sample (NIS). Methods: Using 2018 NIS database, we queried for adults over 18 years with the diagnosis of acute RHF and RHC as a procedure using the ICD-10 code via STATA program. Multivariate logistic regression method was used to adjust for age, gender, race, Charlson comorbidity index, cardiogenic shock, septic shock, respiratory failure, acute coronary syndrome, heart failure, atrial fibrillation/flutter, acute kidney injury, chronic kidney disease, end-stage renal disease. Using a 95% confidence interval (CI), a p-value less than 0.05 was considered statistically significant. Results: A total of 49010 admissions was recorded for acute RHF of which 4795 underwent RHC. 360 patients (7.5%) died in the RHC group versus 4615 (10.4%) in the non-RHC group.16.9% of patients in the RHC group had cardiogenic shock versus 7.3% in the non-RHF group. On univariate analysis, patients undergoing RHC had decreased odds of mortality compared to patients without RHC [Odds ratio (OR) = 0.69, p=0.003] and patients undergoing RHC had increased LOS compared to patients without RHC [OR= 3.15, p=0.012]. The mean LOS for the RHF group was 13.3 days versus 7.5 days in the non-RHF group. On multivariate analysis, those undergoing RHC had decreased odds of mortality compared to those without RHC [OR= 0.47, p=0.000] and LOS was longer for those undergoing RHC [OR= 3.15, p=0.008]. All the outcomes were statistically significant. Conclusion: Right heart catheterization, when used in acute right failure, showed decreased odds of mortality when compared to patients receiving non-invasive medical management only however, no difference in length of stay was observed.
Abstract 10550: Higher Endocardial Viability Ratio is Associated With Improved Left Ventricular Function After Transcatheter Aortic Valve Replacement
Authors: Christian Selinski, Jarred Strickling, Stephanie Katz, Khadijah Breathett, Nishaki M Mehta, Younghoon Kwon, David S Lim, Nishtha Sodhi, Michael Ragosta, Kenneth C Bilchick, Angela Taylor, Sula Mazimba
Journal: Circulation (2022)

Introduction: Both LV dysfunction and AS lead to an increase in LVEDP, a decrease in oxygen delivery to cardiac muscle, and ultimately a decrease in the EVR. Hypothesis: We hypothesized that patients with low EVR would have less significant recovery of LV function after TAVR. Methods: Patients with LVEF &lt;40% and severe AS undergoing TAVR at the University of Virginia (UVA) between 2012 and 2019 were retrospectively reviewed. EVR was calculated by dividing the diastolic pressure time index (DPTI) [(Diastolic blood pressure – LVEDP) x (60seconds/ heart rate – 0.2 seconds)] by the tension time index (TTI) [systolic pressure x 0.2 seconds] using catheter-derived hemodynamics prior to TAVR. LVEF and mAG values were obtained from TTE measurements done for procedural planning and at, or closest to, 1-year follow-up. The patients were divided into cohorts based on EVR above or below 0.7, a value indicative of subendocardial ischemia. Mean change in LVEF was evaluated between these two groups (Figure [1] and Table [1]) and multivariable regression was performed using pre-procedural LVEF, EVR, and change in mean aortic gradient as shown in Table [2]. Results: 128 patients that underwent TAVR had a LVEF &lt;40%. 85 patients (32.5% female) had complete invasive hemodynamic and echocardiographic data. The mean change in post-TAVR LVEF in the lower subgroup was &lt;5% with a standard deviation of 12.5. In patients with EVR &gt;0.7 there was improvement of LVEF of &gt;10% with a standard deviation of 10.8. Two-tailed t-testing was performed with a corresponding p-value of 0.0181. Multivariable regression on pre-procedural LVEF, pre-procedural EVR, and change in mean AG were all statistically significant. Conclusion: EVR &gt;0.7 is associated with greater improvement in LV function in advanced heart failure patients after TAVR.
Abstract 10240: Lower May Not Be Better: Systolic Blood Pressure and Risk of Major Adverse Limb Events in Patients With Symptomatic Peripheral Artery Disease After Revascularization: Insights From Voyager Pad
Authors: Cullen E Buchanan, Michael Szarek, Sebastian Debus, Manesh R Patel, Mark Nehler, Sonia S Anand, Connie Hess, Judith A Hsia, Eva Muehlhofer, Lloyd P Haskell, Scott D Berkowitz, Rupert Bauersachs, Marc P Bonaca
Journal: Circulation (2022)

Introduction: Blood pressure (BP) trials have established optimal targets for major adverse cardiovascular event (MACE) prevention; however, less intensive BP control (also called permissive hypertension) is sometimes utilized to minimize end organ damage in specific settings such as acute stroke and acute kidney injury. An analysis from ALLHAT found that systolic blood pressure (SBP) &lt;120mmHg was associated with a 26% higher rate of major adverse limb events (MALE) in peripheral artery disease (PAD). Whether this association is present in patients with PAD after lower extremity revascularization (LER) is not well described. Methods: VOYAGER PAD randomized patients with symptomatic PAD after LER to rivaroxaban or placebo. The primary composite endpoint was time to first event of MACE or MALE. BP measurements were obtained at baseline, 1, 3, and every 6 months after enrollment. Associations between average SBP at 1 month after LER and incident MACE and MALE through follow up were evaluated. Splines were estimated in proportional hazard models with adjustment for treatment assignment. Results: SBP measurements at 1 month were available in 6,248 patients. Median (IQR) SBP in mmHg was (126, 114-139). The relationship between SBP after LER and future risk of MACE (Figure, Panel A) shows an apparent increased risk at SBP &lt;90mmHg. The relationship of SBP and MALE appeared linear (Figure, Panel B) with a lower risk at higher SBP and greater risk with SBP below ~120mmHg. For every 5mmHg decrease in SBP there was an associated 7% increase in risk of MALE (HR 1.07, 95% CI 1.05-1.10, p &lt;0.0001). The pattern appeared consistent regardless of index revascularization type (surgical vs endovascular). Conclusion: Patients with PAD are at heightened risk of MALE due to obstructive conduit artery disease. There is an inverse relationship between SBP and MALE after LER. Further investigation into optimal BP targets in patients with PAD are warranted.
Abstract 10736: Statistical Shape Modeling Reveals Anatomic Shape Features Associated With the Outcome of Optimal Medical Therapy in Uncomplicated Type B Aortic Dissection
Authors: Minliang Liu, Hai Dong, Yuxuan Wu, Adam Mazlout, John N Oshinski, Wei Sun, John A Elefteriades, Bradley G Leshnower, Rudolph L Gleason
Journal: Circulation (2022)

Introduction: Currently, Type B aortic dissection (TBAD) without the presence of either organ malperfusion or aortic rupture is managed with optimal medical therapy (OMT) consisting of an aggressive anti-hypertensive medical regimen and surveillance imaging. Although OMT achieves excellent early survival, the long-term outcomes with OMT alone remain poor. In this study, we identified anatomic shape features that correlate with OMT failure and aortic growth rates in uncomplicated TBAD via statistical shape modeling (SSM). Methods: Contrast CT scans of patients with acute uncomplicated TBAD were analyzed from 25 patients who were initially treated with OMT. OMT failure was defined as aortic intervention (surgical or endovascular repair, n = 8). Statistical shape models were constructed using principal component analysis (PCA) and partial least square regression (PLSR) to extract anatomic shape features from the aorta and flap geometries. For 14 of the 25 patients, additional follow-up CT scans (5 to 117 months) were used to quantify the rate of aortic expansion. Results: Four PCA (feature 5: p = 0.048, 12: p = 0.005, 14: p = 0.047, 24: p = 0.038) and two PLSR (feature 1: p = 0.000, 2: p = 0.004) shape features were effective at separating OMT failure patients and patients who were adequately treated with OMT. Two PCA features were moderately correlated with aortic growth rate (correlation coefficient, feature 11; r = 0.579, 21: r = 0.503). A PLSR feature was correlated with the growth rate (r = 0.867). Representative shape features are shown in Figure 1. Conclusions: Anatomic shape features extracted from SSM were correlated with the outcomes of OMT and aortic growth rate. SSM shape features may provide additional anatomic risk factors in addition to aortic diameter that predicts aneurysmal degeneration and the need for surgical intervention. Future investigations will incorporate the SSM shape features to determine the risk of OMT failure in uncomplicated TBAD patients.
Abstract 10414: Sesn2/AMPK Signaling Medicates Metformin's Pharmacological Action on Cardiac Mitochondrial Functional Integrity in Response to Ischemic Insults
Authors: Zehui Li, Lauryn Bates, Meredith Krause-Hauch, Hao Wang, Linda Ines Zoungrana, Qun Chen, Di Ren, Edward J Lesnefsky, Ji Li
Journal: Circulation (2022)

Introduction: Metformin activates AMP-activated protein kinase (AMPK) to limit cardiac damage caused by ischemia and reperfusion (I/R). We found that a stress inducible protein Sesn2 is associated with AMPK to maintain mitochondrial oxidative phosphorylation (OXPHOS) during I/R. But the role of Sesn2/AMPK complex in the beneficial effects of metformin on ischemic insults remain unknown. Hypothesis: Metformin modulates Sesn2/AMPK signaling cascade to maintain mitochondrial integrity and respiration functions during I/R stress. Methods: Cardiomyocyte specific Sesn2 knock out (cSesn2 -/- ) and wildtype littermates (Sesn2 f/f ) C57BL/6J mice were subjected to in vivo regional ischemia of 45 min followed by injection of metformin (2 mM, i.v.) 5 min before 24 hr of reperfusion. Mitochondrial functions were determined by a Seahorse XF24 Analyzer. The sarcomere shortening and calcium transients of cardiomyocytes were measured with IonOptix Calcium and Contractility System. Results: Echocardiography data showed that I/R versus sham operations significantly reduced ejection fraction (EF) and fractional shortening (FS) in both Sesn2 f/f and cSesn2 -/- mice. Metformin treatment improved cardiac function under I/R and reduced myocardial infarct size by I/R in Sesn2 f/f but not cSesn2 -/- mice. Immunoblotting data showed metformin activated AMPK signaling and augmented mitochondrial OXPHOS Complex II levels in Sesn2 f/f but not cSesn2 -/- hearts under I/R stress conditions. Transmission electronic microscopy with immuno-gold labeling showed that Sesn2 is primarily located in the mitochondrial membrane and metformin treatment stabilized mitochondrial Sesn2 in Sesn2 f/f versus cSesn2 -/- hearts under I/R conditions. IonOptix measurements showed that metformin rescues contractile dysfunctions and impaired calcium flux by I/R in Sens2 f/f but not cSesn2 -/- cardiomyocytes. In addition, metformin treatment reduced reactive oxygen species (ROS) levels and improved mitochondrial respiration rate under I/R conditions in Sesn2 f/f but not cSesn2 -/- hearts. Conclusions: Administration of metformin benefits cardiac functions under I/R stress. Sesn2/AMPK signaling mediates mitochondrial functional integrity during I/R with metformin treatment.